This first validation of the International Myeloma Working Group geriatric assessment in 125 newly diagnosed multiple myeloma patients was performed using the International Myeloma Working Group ...score based on age, the Charlson Comorbidity Index and cognitive and physical conditions (Activities of Daily Living / Instrumental Activities of Daily Living) to classify patients as fit, intermediate-fit or frail. We verified the International Myeloma Working Group score's impact on outcome, and whether additional tools complement it. Since our prior analyses determined renal, lung and Karnofsky performance impairment as multivariate risks, and the inclusion of frailty, age and cytogenetics complements this, we included the revised myeloma comorbidity index, the Charlson Comorbidity Index, the Hematopoietic Cell Transplantation-Comorbidity Index and the Kaplan-Feinstein Index in this assessment. Multivariate analysis confirmed cytogenetics, Activities of Daily Living, Instrumental Activities of Daily Living and the Charlson Comorbidity Index as risks: 3-year overall survival for fit, intermediate-fit and frail patients was 91%, 77% and 47%, respectively. Using the Charlson Comorbidity Index, the Hematopoietic Cell Transplantation-Comorbidity Index, the Kaplan-Feinstein Index and the revised Myeloma Comorbidity Index allowed us to define fit and frail patients with distinct progression-free and overall survival rates, with the most pronounced differences evidenced via the International Myeloma Working Group score, the Charlson Comorbidity Index and the revised Myeloma Comorbidity Index. Since the Charlson Comorbidity Index is included in the International Myeloma Working Group score, we propose the latter and the revised Myeloma Comorbidity Index for future frailty measurements. Both are useful instruments for identifying myeloma patients with a geriatric risk profile and have a strong prognostic value for functional decline and overall survival. The study was registered as: (clinicaltrials.gov Identifier: 00003686).
Vessel wall imaging (VWI) using T1 dark blood MRI can depict inflammation of intracranial arteries in patients with cerebral vasculitis. Recently, 3D VWI sequences were introduced at 3 Tesla. We ...aimed to compare 2D and 3D VWI for detection of intracranial vessel wall enhancement (VWE) in patients suspected of cerebral vasculitis.
44 MRI scans of 39 patients were assessed that included bi-planar 2D T1 and whole-brain 3D T1 SPACE dark blood VWI pre and post contrast. Visibility and VWE were analyzed in 31 pre-specified intracranial artery segments. Additionally, leptomeningeal and parenchymal contrast enhancement was assessed.
Overall, more arterial segments were visualized with 3D VWI (p<0.0001). Detection of VWE showed fair agreement between 2D and 3D VWI (κ = 0.583). On segmental level, more VWE was detected in intradural ICA by 2D VWI (p<0.001) and in VA V4 segment by 3D VWI (p<0.05). 3D VWI showed more leptomeningeal (p<0.05) and parenchymal (p<0.01) contrast enhancement. In patients with positive diagnosis of cerebral vasculitis, sensitivity was of 67% (2D and 3D VWI) and specificity was 44% (2D VWI) and 48% (3D VWI); more VWE was seen in arteries distal to VA and ICA compared to non-vasculitic patients.
2D and 3D VWI differed in the ability to detect VWE. Whole brain coverage with better evaluability of VAs and distal intracranial artery segments, and depiction of more parenchymal and leptomeningeal enhancement make 3D VWI more favorable. As VWE in arteries distal to VA and ICA may be used for discrimination of vasculitic and non-vasculitic patients, future increase in spatial resolution of 3D VWI sequences may be beneficial.
With growing numbers of elderly multiple myeloma patients, reliable tools to assess their vulnerability are required. The objective of the analysis herein was to develop and validate an easy to use ...myeloma risk score (revised Myeloma Comorbidity Index) that allows for risk prediction of overall survival and progression-free survival differences in a large patient cohort. We conducted a comprehensive comorbidity, frailty and disability evaluation in 801 consecutive myeloma patients, including comorbidity risks obtained at diagnosis. The cohort was examined within a training and validation set. Multivariate analysis determined renal, lung and Karnofsky Performance Status impairment, frailty and age as significant risks for overall survival. These were combined in a weighted revised Myeloma Comorbidity Index, allowing for the identification of fit (revised Myeloma Comorbidity Index ≤3 n=247, 30.8%), intermediate-fit (revised Myeloma Comorbidity Index 4-6 n=446, 55.7%) and frail patients (revised Myeloma Comorbidity Index >6 n=108, 13.5%): these subgroups, confirmed
validation analysis, showed median overall survival rates of 10.1, 4.4 and 1.2 years, respectively. The revised Myeloma Comorbidity Index was compared to other commonly used comorbidity indices (Charlson Comorbidity Index, Hematopoietic Cell Transplantation-Specific Comorbidity Index, Kaplan-Feinstein Index): if each were divided in risk groups based on 25% and 75% quartiles, highest hazard ratios, best prediction and Brier scores were achieved with the revised Myeloma Comorbidity Index. The advantages of the revised Myeloma Comorbidity Index include its accurate assessment of patients' physical conditions and simple clinical applicability. We propose the revised Myeloma Comorbidity Index to be tested with the "reference" International Myeloma Working Group frailty score in multicenter analyses and future clinical trials. The study was registered at the German Clinical Trials Register (DRKS-00003868).
This pilot trial aimed to investigate whether modified short-term fasting (mSTF) reduces the incidence of chemotherapy-induced toxicities and whether an initial ketogenic diet (KD) as fasting ...supportive diet reduces fasting-related discomfort and improves the compliance.
In this controlled cross-over trial, gynaecologic cancer patients undergoing chemotherapy with a minimum of 4 cycles fasted for 96 h during half of their chemotherapy cycles and consumed a normocaloric diet during the other chemotherapy cycles. The caloric intake during mSTF was restricted to 25% of each patient's daily requirement. In addition, half of the patients should eat a 6-day normocaloric KD prior to each mSTF period to investigate a KD's hunger-suppression effect. Chemotherapy-induced toxicities, fasting-related discomfort, body composition, quality of life, laboratory values, and compliance were assessed at each chemotherapy.
Thirty patients aged 30-74 years (median 54 years) completed the study. During mSTF the frequency and severity score of stomatitis - 0.16 ± 0.06; 95% CI -0.28 - (- 0.03); P = 0.013, headaches - 1.80 ± 0.55; 95% CI -2.89 - (- 0.71); P = 0.002, weakness - 1.99 ± 0.87; 95% CI -3.72 - (- 0.26); P = 0.024 and the total toxicities' score were significantly reduced - 10.36 ± 4.44; 95% CI -19.22 - (- 1.50); P = 0.023. We also observed significantly fewer chemotherapy postponements post-mSTF, reflecting improved tolerance of chemotherapy - 0.80 ± 0.37; 95% CI -1.53 - (- 0.06); P = 0.034. A significant reduction in mean body weight by - 0.79 ± 1.47 kg during mSTF was not compensated and remained until study's conclusion (P < 0.005). On average, Insulin - 169.4 ± 44.1; 95% CI -257.1 - (- 81.8); P < 0.001 and Insulin-like growth factor 1 levels - 33.3 ± 5.4; 95% CI -44.1 - (- 22.5); P < 0.001 dropped significantly during fasting. The KD as a fasting supportive diet neither reduced fasting-related discomfort nor improved compliance of our fasting regimen.
MSTF is safe and feasible in gynaecologic cancer patients. Our results indicate that mSTF during chemotherapy can reduce chemotherapy-induced toxicities and enhance the tolerance of chemotherapy. Larger clinical trials are required to recommend mSTF for cancer patients.
germanctr.de: DRKS00011610, registered 30 January, 2017.
Despite significantly improved survival and response rates in patients diagnosed with multiple myeloma, it still remains an incurable disease with a poor outcome, especially in high-risk groups. ...Allogeneic stem cell transplantation offers a potentially curative option but remains controversial due to considerable treatment-related toxicity. We analyzed 109 consecutive myeloma patients who had received reduced-intensity conditioning allogeneic transplantation at the Freiburg University Medical Center between 2000 and 2016. Although most patients were heavily pre-treated in high-risk constellations, the overall response rate was high with 70%, the median overall survival (OS) 39.2%, and the median progression-free survival (PFS) 14.2 months, with a median follow up of 71.5 months. Survival was significantly better in patients with response to previous therapies than in those with progressive disease (median OS 65
11.5 months,
=0.003; median PFS 18.4
5.1 months,
=0.001). Moreover, survival of patients transplanted in first-line was significantly prolonged compared to relapsed/refractory disease (median OS not reached
21.6 months,
<0.001; median PFS 47.7
9.6 months,
<0.001). The non-relapse mortality was relatively low with a cumulative incidence of 12.4% at ten years. Acute graft-
-host disease (GvHD) grade II-IV was observed in 25%, and moderate or severe chronic GvHD in 24%. Quality of life (QoL) assessed with the revised Myeloma Comorbidity Index before and after transplantation remained unchanged. Our data suggest that allogeneic transplantation in the context of novel immunotherapeutic approaches may enable long-term survival and even a potential cure in a carefully selected subgroup of high-risk multiple myeloma patients with acceptable toxicity and preserved QoL.
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